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Biomedical subjects

A Sinha

Publications and source records attributed to A Sinha.

At least 19 recordsLinked to original sources
PubMed1995

Zinc supplementation in young children with acute diarrhea in India.

BACKGROUND: In developing countries the duration and severity of diarrheal illnesses are greatest among infants and young children with malnutrition and impaired immune status, both factors that may be associated with zinc deficiency. In children with severe zinc deficiency, diarrhea is common and responds quickly to zinc supplementation. METHODS: To evaluate the effects of daily supplementation with 20 mg of elemental zinc on the duration and severity of acute diarrhea, we conducted a double-blind, randomized, controlled trial involving 937 children, 6 to 35 months of age, in New Delhi, India. All the children also received oral rehydration therapy and vitamin supplements. RESULTS: Among the children who received zinc supplementation, there was a 23 percent reduction (95 percent confidence interval, 12 percent to 32 percent) in the risk of continued diarrhea. Estimates of the likelihood of recovery according to the day of zinc supplementation revealed a reduction of 7 percent (95 percent confidence interval, -9 percent to +22 percent) in the risk of continued diarrhea during days 1 through 3 and a reduction of 38 percent (95 percent confidence interval, 27 percent to 48 percent) after day 3. When zinc supplementation was initiated within three days of the onset of diarrhea, there was a 39 percent reduction (95 percent confidence interval, 7 percent to 61 percent) in the proportion of episodes lasting more than seven days. In the zinc-supplementation group there was a decrease of 39 percent (95 percent confidence interval, 6 percent to 70 percent) in the mean number of watery stools per day (P = 0.02) and a decrease of 21 percent (95 percent confidence interval, 10 percent to 31 percent) in the number of days with watery diarrhea. The reductions in the duration and severity of diarrhea were greater in children with stunted growth than in those with normal growth. CONCLUSION: For infants and young children with acute diarrhea, zinc supplementation results in clinically important reductions in the duration and severity of diarrhea.

Acute Disease↗
PubMed1995

A study on estimation of age from pubic symphysis.

The present study has been carried on 82 pairs of pubic symphysis collected from fresh male cadavers. Various features were noted on the symphyseal surface--ridges and furrows, dorsal margin, ventral bevelling, lower extremity, ossific nodule, upper extremity, ventral rampart, dorsal plateau and symphyseal rim. Varying combination of these features were used as criteria for age estimation of the subjects.

Adolescent↗
PubMed1995

Purification, characterization and antitumor activity of L-asparaginase isolated from Pseudomonas stutzeri MB-405.

An L-asparaginase produced by Pseudomonas stutzeri MB-405 was isolated and characterized. After initial ammonium sulfate fractionation, the enzyme was purified by consecutive column chromatography on Sephadex G-100, Ca-hydroxylapatite, and DEAE-Sephadex A-50. The 665.5-fold purified enzyme thus obtained has the specific activity of 732.3 units mg protein-1 with an overall recovery of 27.2%. The apparent M(r) of the enzyme under nondenaturing and denaturing conditions was 34 kDa and 33 kDa respectively, and the isoelectric point was 6.38 +/- 0.02. It displayed optimum activity at pH 9.0 and 37 degrees C. The enzyme was very specific for L-asparagine and did not hydrolyze L-glutaminate. The Km of the L-asparaginase was found to be 1.45 x 10(-4) M towards L-asparagine and was competitively inhibited by 5-diazo-4-oxo-L- norvaline (DONV) with a Ki of 0.03 mM. Metal ions such as Mn2+, Zn2+, Hg2+, Fe3+, Ni2+, and Cd2+ potentially inhibited the enzyme activity. The activity was enhanced in the presence of thiol-protecting reagents such as DTT, 2-ME, and glutathione (reduced), but inhibited by PCMB and iodoacetamide. The tumor inhibition study with Dalton's lymphoma tumor cells in vivo indicated that this enzyme possesses antitumor properties.

Amino Acids↗
PubMed1995

Dopamine D3-preferring ligands act at synthesis modulating autoreceptors.

Several compounds exist that demonstrate a binding preference for cloned dopamine D3 receptors vs. D2 receptors, including (+/-)7-OH DPAT, (+)-UH232 and (+)-AJ76. Inasmuch as recent evidence suggests that the dopamine D3 receptor may function as a dopamine autoreceptor, we have investigated the ability of these D3-preferring ligands to act at synthesis modulating dopamine autoreceptors using the gamma-butyro-lactone model in vivo to isolate the presynaptic effects of (+/-)7-OH DPAT, (+)-UH232 and (+)-AJ76. Further, given the discrete anatomical distribution of the D3 receptor, the striatum, n. Accumbens, and olfactory tubercles were examined for comparative analyses. (+/-)7-OH DPAT displayed agonist characteristics at synthesis modulating dopamine autoreceptors with a greater potency in the olfactory tubercle vs. either the striatum or the nucleus accumbens (ED-50 values were 31.8, 38.1 and 10.2 micrograms/kg for the striatum, nucleus accumbens and olfactory tubercles, respectively). Further, (+)-UH232 and (+)-AJ76 attenuated the effects of (+/-)7-OH DPAT (60 micrograms/kg s.c.) in all three regions examined. However, the effects of (+/-)7-OH DPAT were antagonized to a lesser extent in the olfactory tubercles than in either the striatum or the nucleus accumbens. Given the relative abundance of D3 receptors in the olfactory tubercles, the data are consistent with the notion that (+/-)7-OH DPAT may exert its autoreceptor effects preferentially through dopamine D3 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Complementary effects of pravastatin and nicotinic acid in the treatment of combined hyperlipidaemia in diabetic and non-diabetic patients.

BACKGROUND: Given that treatment with a single drug is frequently unsuccessful in patients with combined hyperlipidaemia, there is a rationale for the study of regimens using drugs that have complementary therapeutic profiles. We therefore set out to compare the efficacy of a combined pravastatin and nicotinic acid regimen with higher dose monotherapy using either drug in patients with non-insulin-dependent diabetes and in non-diabetic patients with combined hyperlipidaemia. METHODS: Forty-four patients with total-cholesterol levels of 6.5 mmol/l or higher and triglyceride levels of 2.5 mmol/l or above were randomly assigned to receive either pravastatin alone (40mg/day) or nicotinic acid alone (1500mg/day) for 12 weeks. At the end of this period, the participants received a combination of pravastatin (20mg/day) and nicotinic acid (1000mg/day) for a further 12 weeks. The lipid parameters measured included levels of total cholesterol, triglycerides, low-density-lipoprotein (LDL) cholesterol and high-density-lipoprotein (HDL) cholesterol. RESULTS: Thirty-three patients (22 without and 11 with diabetes) completed the protocol. Monotherapy with pravastatin was more effective than that with nicotinic acid in reducing levels of total cholesterol (-24.9 versus -9.8%, P<0.001) and LDL cholesterol (-32.1 versus -16.9%, P < 0.01), similar in reducing levels of triglyceride (-28.0 versus -31.8%, NS) and tended to be less effective in elevating levels of HDL cholesterol (+16.4 versus +30.8%, P = 0.06). Combination therapy was more effective than pravastatin monotherapy in reducing levels of triglyceride (-39.3 versus -28.0%, P < 0.05) and elevating those of HDL cholesterol (+35.6 versus +16.4%, P < 0.001) and was equally effective in reducing total-cholesterol (-22.3 versus -24.9%, NS) and LDL-cholesterol (-27.1 versus -32.1%, NS) levels. Combination therapy was more effective than nicotinic acid monotherapy in reducing levels of total cholesterol (-23.8 versus -9.8%, P < 0.001), triglyceride (-39.4 versus -31.8%, P < 0.05) and LDL cholesterol (-35.7 versus -16.9%, P < 0.05) and equally effective in elevating HDL-cholesterol levels (+33.6 versus +30.8%, NS). Diabetic and non-diabetic participants responded similarly to combination therapy. Eleven patients (25%) were withdrawn from the study: nine as a result of nicotinic acid intolerance (flushing and nausea) and one through pravastatin intolerance (nausea); one patient died of a myocardial infarction. Combination therapy elevated glycosylated haemoglobin A1c levels in non-diabetic patients (5.5 to 5.8%, P < 0.001); in diabetic patients, however, the observed rise (7.4 to 7.9%) was not statistically significant. Fasting plasma glucose levels, liver function tests and levels of creatine kinase or uric acid were unaffected by either monotherapy or by combination therapy, with the exception of an elevation of the glucose level in diabetic patients receiving nicotinic acid monotherapy. CONCLUSION: Pravastatin and nicotinic acid in lower-dose combination are more effective than pravastatin alone in reducing levels of triglyceride and elevating those of HDL cholesterol and are more effective than nicotinic acid alone in reducing total-cholesterol triglyceride and LDL-cholesterol levels. Combination therapy is equally effective in type-II diabetic and non-diabetic people. The complementary effects of the combination therapy on lipid levels suggest that this regimen should be considered as a therapeutic option in patients with combined hyperlipidaemia who tolerate the side effects of nicotinic acid.

Adult↗
PubMed1992

Induction of specific enzymes of the oxidative pentose phosphate pathway by glucono-delta-lactone in Saccharomyces cerevisiae.

Growth of Saccharomyces cerevisiae on D-glucono-delta-lactone (delta gl) was found to be associated with a specific coordinate induction of the synthesis of two enzymes of the oxidative pentose phosphate pathway--6-phosphogluconate dehydrogenase and 6-phosphogluconolactonase--together with that of a third enzyme, gluconokinase. The gnd1 mutation, responsible for an approximately 80% loss of 6-phosphogluconate dehydrogenase activity and the inability of the cells to grow on delta gl, completely abolished the induction of all three enzymes, while the gnd2 mutation affected this only partially. One class of gnd1 revertants, selected for growth on delta gl, was found to have recovered normal dehydrogenase activity and the ability to synthesize the three enzymes when induced by delta gl. Another class of delta gl-positive revertants possessed constitutively elevated levels of gluconokinase. In contrast, glucose-positive revertants of gnd1, with restored constitutive dehydrogenase activity, continued to remain deficient in induction of the three enzymes and also failed to grow on delta gl. Induction of 6-phosphogluconate dehydrogenase activity was associated with increased transcription of the gene coding for the major isoenzyme; the transcript remained undetectable in the gnd1 mutant. Induction of these specific enzymes thus appears to be essential for growth of S. cerevisiae on delta gl.

Carboxylic Ester Hydrolases↗
PubMed1992

Effect of Vibrio cholerae-L-asparaginase on surface structure of splenic lymphocytes.

The surface ultrastructure of splenic lymphocytes and rosetting properties of lymphocytes of Swiss mice were studied under scanning electron microscope following transplantation of Dalton's lymphoma and ascites fibrosarcoma tumour cells and administration of Vibrio cholerae-L-asparaginase. The results were compared to those obtained with the standard Escherichia coli-L-asparaginase. The surface structure of the lymphocytes (T cells) following L-asparaginase administration was not so different from that of normal lymphocytes. V. cholerae-L-asparaginase did not cause higher number of rosette formation in T cells as compared to the normal group. The study thus revealed that V. cholerae-L-asparaginase did not have a significant stimulatory or non-immunosuppressive effect on the lymphocyte functions.

Animals↗
PubMed1991

Sheep erythrocytes provide metabolic triggers for tumour phagocytosis in polymorphonuclear neutrophils: a possible mechanism of tumour inhibition in mice.

Intraperitoneal (i.p.) injection of 7% Sheep Erythrocytes (SRBC) was found to inhibit growth of a transplanted tumour and exhibit a consequent increase in total survival compared to untreated tumour controls. In an attempt to probe into the mechanism(s) involved, functional aspects of Polymorphonuclear Neutrophils (PMNs) were investigated in terms of their 'metabolic (respiratory) burst' during tumour phagocytosis. Both NADPH-Oxidase mediated superoxide anion (O2-.) formation (NBT reduction) and Myeloperoxidase (MPO) mediated oxidisable halide incorporation (131I incorporation) were found to be highly stimulated by SRBC in normal (CS) and tumour bearing counterparts (TS). A little tumour mediated residual inhibition persists on the MPO system in PMNs of animals with tumour plus SRBC (TS) which, however, showed an obvious bonus effect over the tumour controls (TC). The results suggest a possible mechanism of tumour inhibition by SRBC in mice with the involvement of highly stimulated phagocytic metabolism in PMNs.

Animals↗
PubMed1991

Induction of L-asparaginase synthesis in Vibrio proteus.

Studies on L-asparaginase synthesis in V. proteus showed increased synthesis in cultures grown under conditions of moderate aeration (P less than 0.005) after oxygen had been used up from the medium. Addition of sodium lactate to the medium at a concentration of 80 mu mole/ml, stimulated L-asparaginase synthesis (2.2 times over control) in moderately-aerated cultures (P less than 0.001). The substrate L-asparagine induced enzyme synthesis when growth conditions were made anaerobic or lactate was incorporated into the medium (3.8 times increased enzyme synthesis over control).

Asparaginase↗
PubMed1991

Infant growth in relation to feeding practices in low income families.

A survey of feeding practices and measurements of weight, length and chest circumference of infants upto the age of 12 months and belonging to low income families of some selected villages at Pantnagar was carried out during 1987-88. The study revealed that as many as 83% of infants were exclusively breast fed up to the age of 6 months. In addition to being breast fed, 77% of infants between 9 and 12 months were also receiving semi-solids. Very small quantities of cereals, pulses, biscuits and fruits were reported to be the supplementary foods fed to infants. Animal milk diluted to varying degrees was fed as a supplement by some mothers and as a substitute by a few. Growth patterns of various feed types in terms of the anthropometric measurements were not found significantly different in different feeding practices. With reference to International standards (NCHS), it was seen that weight of only 25% of male and 55% of female infants fell in the normal range at the age of 3 months and this percentage declined from 3rd month to 12th month of age. Though the percentage falling in normal range was higher for length, the pattern of decline with the advancement in age was similar. This unsatisfactory growth performance of even those who received other foods along with breast milk is indicative of the fact that the quantity/quality of supplementary foods (along with other factors) were not sufficient to promote normal growth.

Anthropometry↗
PubMed1990

The effects of sorbinil, an aldose reductase inhibitor, on the corneal endothelium in galactosemic dogs.

Wide-field specular microscopy was used to examine the central corneal endothelium of age- and sex-matched beagle dogs fed for up to 32 months either normal control diets containing 30% nonnutrient filler (13 dogs) or diets containing 30% galactose with (13 dogs) or without (12 dogs) concomitant treatment with the aldose reductase inhibitor, sorbinil. Computerized morphometric analysis of the endothelial cells indicated that a significant decrease in cell density and increase in mean cell area occurred in untreated galactose-fed dogs after 32 months of feeding compared with the normal controls. However, no significant difference could be observed in similar galactose-fed dogs treated with sorbinil. No significant difference in the coefficient of variation of the area, or percent hexagonality of the endothelial cells, or the corneal thickness could be observed in any group. These findings demonstrated that endothelial abnormalities were present in the cornea of the galactose-fed dogs which were similar to those reported for diabetic dogs, rats, and patients and that these changes can be prevented by the concomitant administration of an aldose reductase inhibitor. These findings suggest a role for aldose reductase in the abnormalities noted in the corneal endothelium in diabetes and galactosemia.

Aldehyde Reductase↗
PubMed1990

A fish oil diet preserves renal function in nephrotoxic serum nephritis.

Fish oil diets preserve renal function in murine lupus, but we have found that these diets accelerate renal deterioration in renoprival nephropathy. In this study we examined the effects of dietary fish oil in accelerated nephrotoxic serum nephritis. For 1 month, 14 female rats were fed diets that differed only in fat composition, containing either menhaden (fish) oil or beef tallow (control). Rats were then preimmunized with rabbit IgG and, 5 days later, were injected with nephrotoxic serum. Glomerular filtration rate (GFR) was measured continuously in conscious animals by means of intraperitoneal 14C-labeled inulin minipumps. Fish oil-containing diets markedly attenuated the nephrotoxic serum-induced decline in GFR and the rise in proteinuria and significantly reduced glomerular prostaglandin E2 and thromboxane A2. The results of tests of renal histology showed no differences between the two groups. Five days after preimmunization, rats fed fish oil had more rabbit IgG remaining in their serum and had mounted less of an antibody response to the rabbit IgG. Fish oil diets also resulted in an attenuated disappearance of injected 14C-labeled rabbit IgG. In vitro, peritoneal macrophages from rats fed fish oil took up less rabbit IgG than macrophages from rats fed control diets. Thus the beneficial effects of a fish oil diet may result from defective immune surveillance and from alterations in eicosanoids.

Animals↗
PubMed1987

Comparative functional analysis of helper T lymphocyte responses to soluble and particulate antigens.

An adaptable and sensitive assay to analyze the roles of helper T lymphocytes (TH) which recognize soluble or cell-surface bound antigens in the induction of cytotoxic T lymphocyte precursors (CTLp) is described. Long-term T cell lines that recognize purified protein derivative, keyhole limpet hemocyanin, or Corynebacterium parvum were used in these studies. The ability of T cells from these lines to induce cytotoxic T lymphocyte or antibody responses were compared with their ability to proliferate or release interleukin 2 (IL 2). The results demonstrate that these T cell lines are able to react to soluble antigen by proliferation and IL 2 release. Moreover, the same cell lines are able to interact with CTLp or with the precursors of antibody-secreting B cells to induce a response. In the induction of CTLp we observed an inverse correlation between the number of TH cells required and the concentration of antigen used to pulse the antigen presenting cells. However the correlation between the ability of TH lines to proliferate specifically in response to antigen and to act as helpers for CTLp and B cells was not absolute as cells with compromised proliferative capacity were able to efficiently deliver inductive signals.

Animals↗
PubMed1986

Specific immunosuppression by immunotoxins containing daunomycin.

Daunomycin, when conjugated with a targeting antigen by an acid-sensitive spacer, remains inactive at the intravascular pH of 7 but becomes active after cleavage within the acidic lysosomal environment of the target cell. This observation made it possible to construct cytocidal compounds that caused antigen-specific suppression of murine lymphocyte function. When daunomycin was coupled to the hapten conjugate of ovalbumin by an acid-sensitive cis-aconityl group, it caused hapten-specific impairment of immunocompetence in murine B lymphocytes in vitro and in vivo. Furthermore, the response by T lymphocytes to concanavalin A in vitro was selectively eliminated by a conjugate between daunomycin plus the acid-sensitive spacer and a monoclonal antibody specific for T cells.

Animals↗